Metformin acts as an energy regulator by activating 5'-adenosine monophosphate-activated protein kinase (AMPK), which is a key player in the regulation of energy homeostasis, but it is uncertain whether AMPK is its direct target. This study aims to investigate the possible interaction between metformin and AMPK. First, we verified that metformin can promote AMPK activation and induce ACC inactivation in human HepG2 cells using western blot. Then we predicted that metformin may interact with the γ subunit of AMPK by molecular docking analysis. The fluorescence spectrum and ForteBio assays indicated that metformin has a stronger binding ability to the γ subunit of AMPK than to α subunit. In addition, interaction of metformin with γ-AMPK resulted in a decrease in the α-helicity determined by CD spectra, but relatively little change was seen with α-AMPK. These results demonstrate that metformin may interact with AMPK through binding to the γ subunit.

Background Sepsis is a primary global health threat and costs a lot, requiring effective and affordable treatments. We performed this meta-analysis to explore the treatment of hydrocortisone, ascorbic acid, and thiamine (HAT) in sepsis and septic shock. Methods We searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 14, 2021. We included randomized controlled trials (RCTs) that evaluated the HAT treatments in sepsis and septic shock. The primary outcome was the change in SOFA score over the 72 h. The second outcomes were the hospital, and 28-/30-day mortality, the duration of vasopressors, PCT clearance, hospital length of stay (LOS), and ICU LOS. We performed a subgroup analysis and a trial sequential analysis (TSA). The Der Simonian–Laird random-effects models were used to report the pooled risk ratios (RR) or mean difference (MD) with confidence intervals (CI). Results Nine RCTs, enrolling 1427 patients of sepsis and septic shock treated with HAT (717) or only standard care (710), were included. There was a significant difference between the two groups in the change in SOFA score over the first 72 h (MD 0.65, 95% CI 0.30 to 1.00), the duration of vasopressors (MD − 18.16, 95% CI − 25.65 to − 10.68) and the PCT clearance (MD 14.54, 95% CI 0.64 to 28.43). In addition, there was no significant difference in the hospital mortality (RR 1.07, 95% CI 0.85 to 1.34), the 28-/30-day mortality (RR 0.96, 95% CI 0.80 to 1.15), the hospital LOS (MD 0.78, 95% CI − 0.30 to 1.86), and ICU LOS (MD 0.12, 95% CI − 0.53 to 0.78). Conclusions The HAT combination improves the SOFA score in the first 72 h and reduces the duration of vasopressors in patients with sepsis. Given the minor mean difference of the change in SOFA score, the mortality benefit has not been observed. Trial registration PROSPERO, CRD42020203166.

Objective This study aimed to present the case of a boy with acute distress syndrome (ARDS) treated with low-dose umbilical cord blood (UCB) therapy and explore the underlying possible mechanism. Methods A 7-year-old boy with severe Pneumocystis carinii pneumonia and severe ARDS was treated with allogeneic UCB as salvage therapy. Results The patient did not improve after being treated with lung protective ventilation, pulmonary surfactant replacement, and extracorporeal membrane oxygenation (ECMO) for 30 days. However, his disease reversed 5 days after allogeneic UCB infusion, and he weaned from ECMO after 7 days of infusion. Bioinformatics confirmed that his Toll-like receptor (TLR) was abnormal before UCB infusion. However, after the infusion, his immune system was activated and repaired, and the TLR4/MyD88/NF-κB signaling pathway was recovered. Conclusion Allogenic UCB could treat ARDS by repairing the TLR4/MyD88/NF-κB signaling pathway, thereby achieving stability of the immune system.

Aim To examine the differences between oxygenation index (OI) and arterial partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2, [P/F]) in evaluating the severity of pediatric acute respiratory distress syndrome (PARDS). Methods The severity of PARDS was graded by using the OI score and P/F ratio, respectively. The data including clinical indexes and prognosis indicators were recorded and analyzed. Results During the 3‐year study period, there were significant differences between OI and P/F scores in the severity grading of PARDS patients (p < .05). However, in severe diseases, both the scorings of OI and P/F were consistent (24.6% vs. 25.6%). The OI scores appeared more accurate when compared with P/F in the correlation between them and the pediatric critical illness score, multiple organ dysfunction syndromes (MODS), pressure indexes of ventilators and patients' prognosis. In the receiver operating characteristic curve, the critical values of OI and P/F were 8.42 and 144.71. Area under the curve of them were 0.839 and 0.853. The sensitivity values were both 0.854. The specificity values were 0.584 and 0.602. Conclusions The OI and P/F were consistent in designating patients with severe PARDS. Among patients with mild to moderate diseases, the P/F could still be used for rapid determination given its simple calculation. Combined with the prognostic factors, the OI score was more accurate.

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